Osteoporosis is a major health problem in postmenopausal women. At age 50, half of women will suffer an osteoporotic fracture in their remaining lifetime [1], causing increased disability and mortality [1, 2]. Vitamin D deficiency, defined as a serum 25(OH)D <15 ng/mL, contributes to osteoporosis via decreased calcium absorption (CaAb), secondary hyperparathyroidism (HPT), increased bone resorption and decreased bone mineral density (BMD) [3]. Thus, experts agree that patients with vitamin D deficiency should receive vitamin D therapy [4-7]. Vitamin D insufficiency (VDI) is a milder form of hypovitaminosis D defined as a 25(OH)D level between 15 and 30 ng/mL regardless of parathyroid hormone (PTH) status [8]. Experts disagree on whether to treat VDI, as the clinical benefits of therapy are uncertain. Some experts [8-11] insist the optimal 25(OH)D level is e30 ng/mL. By contrast, both the Food and Nutrition Board [12] and NIH Evidence Report No. 158 [13] state that insufficient evidence exists to declare the optimal serum 25(OH)D for bone health, despite review of ~170 studies. Consequently, the Food and Nutrition Board cannot determine a recommended daily allowance for vitamin D. Confusion over the optimal 25(OH)D level results, in part, because previous trials failed to recruit subjects based on initial 25(OH)D levels and/or failed to target or achieve 25(OH)D levels e30 ng/mL. Moreover, secondary HPT, the proposed mechanism by which VDI causes bone loss, occurs in only 10% to 33% of people with VDI [14-17]. As such, people with VDI and normal PTH might not experience clinical benefits from vitamin D therapy. VDI is widespread [15, 18, 19], affecting 26% to 39% of postmenopausal American women with [20] and without [21] osteoporosis. Therefore, determining the ideal 25(OH)D level for optimal calcium homeostasis and bone health is of utmost clinical and public health importance. Our overall goal, congruent with Healthy People 2010 objective 2-9, is to evaluate the effect of vitamin D therapy on the risk of osteoporosis in postmenopausal women with VDI, as reflected by changes in CaAb, BMD and muscle fitness. Our second goal is to evaluate whether a high-dose vitamin D regimen, chosen to achieve and maintain a 25(OH)D level e30 ng/mL [17], is superior in its effects on study outcomes compared to a low-dose vitamin D regimen that can permit continued VDI [22-25]. PUBLIC HEALTH RELEVANCE: One in two women past menopause has mildly low vitamin D levels. We don't know if vitamin D therapy helps these women to have stronger bones that break less easily. We also don't know whether high-dose vitamin D therapy is better than low-dose vitamin D, in its effects on calcium absorption, bone calcium levels and muscle function. We will ask 250 women past menopause with mildly low vitamin D levels to take part in a one year study. One third of women will receive placebo, one-third will receive low-dose vitamin D and one-third will receive a high-dose vitamin D tablet that keeps their blood levels above 30 ng/mL. We will compare the changes in calcium CaAb, bone calcium levels and muscle fitness among women receiving placebo, low-dose vitamin D and high- dose vitamin D. This study will help decide whether vitamin D therapy lessens the risk of osteoporosis in postmenopausal women, and at what vitamin D dose those benefits occur.